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Background: Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. Objectives: The aim of this systematic review is to better understand the various aspects of the cardio-vascular complications of COVID-19 by pooling data from a large number of autopsy studies. Data sources: We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published be-tween database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. Study eligibility criteria: Articles were considered eligible for inclusion if they reported human post-mortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. Participants: Confirmed COVID-19 patients with post-mortem cardiovascular findings. Interventions: None. Methods: Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). Results: This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-10 0%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median re-ported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). Conclusions: Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19. (C) 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi , presenting acute and chronic phases where cardiomyopathy, megaesophagus, and/or megacolon stand out. During the course of its life cycle, the parasite has an important gastrointestinal tract transit that leads to severe forms of CD.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate, multiple variants of concern have emerged. New variants pose challenges for diagnostic platforms because sequence diversity can alter primer/probe-binding sites (PBSs), causing false-negative results. The MassARRAY SARS-CoV-2 Panel (Agena Bioscience) uses RT-PCR and mass spectrometry to detect five multiplex targets across N and ORF1ab genes. Herein, we use a data set of 256 SARS-CoV-2-positive specimens collected between April 11, 2021, and August 28, 2021, to evaluate target performance with paired sequencing data. During this time frame, two targets in the N gene (N2 and N3) were subject to the greatest sequence diversity. In specimens with N3 dropout, 69% harbored the Alpha-specific A28095U polymorphism that introduces a 3'-mismatch to the N3 forward PBS and increases risk of target dropout relative to specimens with 28095A (relative risk, 20.02; 95% CI, 11.36 to 35.72; P 0.0001). Furthermore, among specimens with N2 dropout, 90% harbored the Delta-specific G28916U polymorphism that creates a 3'-mismatch to the N2 probe PBS and increases target dropout risk (relative risk, 11.92; 95% CI, 8.17 to 14.06; P 0.0001). These findings highlight the robust capability of MassARRAY SARS-CoV-2 Panel target results to reveal circulating virus diversity, and they underscore the power of multitarget design to capture variants of concern.

We assessed the circulation of severe acute respiratory syndrome coronavirus-2 variants amongst vaccinated military personnel in Bogotá, Colombia to evaluate the mutations of certain variants and their potential for breakthrough infection in vaccinated subjects. We observed that in vaccinated individuals the most frequent infecting lineage was Mu (B.1.621 and B.1.621.1). The above is possibly associated with specific mutations that confer it with vaccine-induced immune escape ability. Our findings highlight the importance of how genomic tracking coupled with epidemiological surveillance can assist in the study of novel emerging variants (e.g., Omicron) and their impact on vaccination efforts worldwide.

The coronavirus disease 2019 (COVID-19) pandemic has sparked the rapid development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics. However, emerging variants pose the risk for target dropout and false-negative results secondary to primer/probe binding site (PBS) mismatches. The Agena MassARRAY® SARS-CoV-2 Panel combines reverse-transcription polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight mass-spectrometry to probe for five targets across N and ORF1ab genes, which provides a robust platform to accommodate PBS mismatches in divergent viruses. Herein, we utilize a deidentified data set of 1262 SARS-CoV-2-positive specimens from Mount Sinai Health System (New York City) from December 2020 to April 2021 to evaluate target results and corresponding sequencing data. Overall, the level of PBS mismatches was greater in specimens with target dropout. Of specimens with N3 target dropout, 57% harbored an A28095T substitution that is highly specific for the Alpha (B.1.1.7) variant of concern. These data highlight the benefit of redundancy in target design and the potential for target performance to illuminate the dynamics of circulating SARS-CoV-2 variants.

SARS-CoV-2 NSP12, the viral RNA-dependent RNA polymerase (RdRp), is required for viral replication and is a therapeutic target to treat COVID-19. To facilitate research on SARS-CoV-2 NSP12 protein, we developed a rat monoclonal antibody (CM12.1) against the NSP12 N-terminus that can facilitate functional studies. Immunoblotting and immunofluorescence assay (IFA) confirmed the specific detection of NSP12 protein by this antibody for cells overexpressing the protein. Although NSP12 is generated from the ORF1ab polyprotein, IFA of human autopsy COVID-19 lung samples revealed NSP12 expression in only a small fraction of lung cells including goblet, club-like, vascular endothelial cells, and a range of immune cells, despite wide-spread tissue expression of spike protein antigen. Similar studies using in vitro infection also generated scant protein detection in cells with established virus replication. These results suggest that NSP12 may have diminished steady-state expression or extensive posttranslation modifications that limit antibody reactivity during SARS-CoV-2 replication.

Alice-in-Wonderland syndrome (AIWS) is a perceptual disorder embracing a spectrum of self-experienced paroxysmal body image illusions including most commonly distortions of shape (metamorphopsia), size (macropsia or micropsia), distance (pelopsia or teleopsia), movement, and color among other visual and somesthetic distortions. Depersonalization, derealization, and auditory hallucinations have also been described. Recent reports suggest that infectious diseases are the predominant etiology for AIWS, especially among children. This article reviews current understanding regarding the association between infection and development of AIWS.

Background Coronavirus disease 2019 (COVID-19) patients manifest with pulmonary symptoms reflected by diffuse alveolar damage (DAD), excessive inflammation, and thromboembolism. The mechanisms mediating these processes remain unclear. Methods We performed multicolor staining for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and lineage markers to define viral tropism and lung pathobiology in 5 autopsy cases. Results Lung parenchyma showed severe DAD with thromboemboli. Viral infection was found in an extensive range of cells including pneumocyte type II, ciliated, goblet, club-like, and endothelial cells. More than 90% of infiltrating immune cells were positive for viral proteins including macrophages, monocytes, neutrophils, natural killer (NK) cells, B cells, and T cells. Most but not all infected cells were angiotensin-converting enzyme 2 (ACE2) positive. The numbers of infected and ACE2-positive cells are associated with extensive tissue damage. Infected tissues exhibited high levels of inflammatory cells including macrophages, monocytes, neutrophils, and NK cells, and low levels of B cells but abundant T cells consisting of mainly T helper cells, few cytotoxic T cells, and no regulatory T cells. Robust interleukin-6 expression was present in most cells, with or without infection. Conclusions In fatal COVID-19 lungs, there are broad SARS-CoV-2 cell tropisms, extensive infiltrated innate immune cells, and activation and depletion of adaptive immune cells, contributing to severe tissue damage, thromboemboli, excess inflammation, and compromised immune responses.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are characterized by differences in transmissibility and response to therapeutics. Therefore, discriminating among them is vital for surveillance, infection prevention, and patient care. While whole viral genome sequencing (WGS) is the “gold standard” for variant identification, molecular variant panels have become increasingly available. Most, however, are based on limited targets and have not undergone comprehensive evaluation. We assessed the diagnostic performance of the highly multiplexed Agena MassARRAY® SARS-CoV-2 Variant Panel v3 to identify variants in a diverse set of 391 SARS-CoV-2 clinical RNA specimens collected across our health systems in New York City, USA as well as in Bogotá, Colombia (September 2, 2020 – March 2, 2022). We demonstrate almost perfect levels of interrater agreement between this assay and WGS for 9 of 11 variant calls (κ ≥ 0.856) and 25 of 30 targets (κ ≥ 0.820) tested on the panel. The assay had a high diagnostic sensitivity (≥93.67%) for contemporary variants (e.g., Iota, Alpha, Delta, Omicron [BA.1 sublineage]) and a high diagnostic specificity for all 11 variants (≥96.15%) and all 30 targets (≥94.34%) tested. Moreover, we highlight distinct target patterns that can be utilized to identify variants not yet defined on the panel including the Omicron BA.2 and other sublineages. These findings exemplify the power of highly multiplexed diagnostic panels to accurately call variants and the potential for target result signatures to elucidate new ones.ImportanceThe continued circulation of SARS-CoV-2 amidst limited surveillance efforts and inconsistent vaccination of populations has resulted in emergence of variants that uniquely impact public health systems. Thus, in conjunction with functional and clinical studies, continuous detection and identification are quintessential to inform diagnostic and public health measures. Furthermore, until WGS becomes more accessible in the clinical microbiology laboratory, the ideal assay for identifying variants must be robust, provide high resolution, and be adaptable to the evolving nature of viruses like SARS-CoV-2. Here, we highlight the diagnostic capabilities of a highly multiplexed commercial assay to identify diverse SARS-CoV-2 lineages that circulated at over September 2, 2020 – March 2, 2022 among patients seeking care at our health systems. This assay demonstrates variant-specific signatures of nucleotide/amino acid polymorphisms and underscores its utility for detection of contemporary and emerging SARS-CoV-2 variants of concern.

We reported the frequency of resistance gene detection in Gram-negative blood culture isolates and correlated these findings with corresponding antibiograms. Data were obtained from 1045 isolates tested on the GenMark Dx ePlex Blood Culture Identification Gram-Negative Panels at the Mount Sinai Hospital Clinical Microbiology Laboratory in New York from March 2019 to February 2021. Susceptibilities were performed using Vitek 2 (bioMérieux Clinical Diagnostics) or Microscan (Beckman Coulter Inc.).

BackgroundSaliva is an optimal specimen for detection of viruses that cause upper respiratory infections including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to its cost-effectiveness and non-invasive collection. However, together with intrinsic enzymes and oral microbiota, children’s unique dietary habits may introduce substances that interfere with diagnostic testing.MethodsTo determine whether children’s dietary choices impact SARS-CoV-2 detection in saliva, we performed a diagnostic study that simulates testing of real-life specimens provided from healthy children (n=5) who self-collected saliva at home before and at 0, 20, and 60 minutes after eating from 20 foods they selected. Each of seventy-two specimens was split into two volumes and spiked with SARS-CoV-2-negative or -positive standards prior to side-by-side testing by reverse-transcription polymerase chain reaction matrix-assisted laser desorption ionization time-of-flight (RT-PCR/MALDI-TOF) assay.ResultsDetection of internal extraction control and SARS-CoV-2 nucleic acids was reduced in replicates of saliva collected at 0 minutes after eating 11 of 20 foods. Interference resolved at 20 and 60 minutes after eating all foods except hot dog in one participant. This represented a significant improvement in detection of nucleic acids compared to saliva collected at 0 minutes after eating (P=0.0005).ConclusionsWe demonstrate successful detection of viral nucleic acids in saliva self-collected by children before and after eating a variety of foods. Fasting is not required before saliva collection for SARS-CoV-2 testing by RT-PCR/MALDI-TOF, but waiting 20 minutes after eating is sufficient for accurate testing. These findings should be considered for SARS-CoV-2 testing and broader viral diagnostics in saliva specimens.

BACKGROUND Cladophialophora bantiana is a dematiaceous, saprophytic fungus and a rare but reported cause of intracranial abscesses due to its strong neurotropism. Although it predominantly affects immunocompetent individuals with environmental exposure, more recently, its significance as a highly lethal opportunistic infection in transplant recipients has been recognized. Successful treatment requires timely but often challenging diagnosis, followed by complete surgical excision. Next-generation sequencing of microbial cell-free DNA (cfDNA) from plasma is a novel diagnostic method with the potential to identify invasive fungal infections more rapidly and less invasively than conventional microbiological testing, including brain biopsy. OBSERVATIONS The authors described the case of a recipient of a liver transplant who presented with seizures and was found to have innumerable ring-enhancing intracranial lesions. The Karius Test, a commercially available method of next-generation sequencing of cfDNA, was used to determine the causative organism. Samples from the patient’s plasma identified C. bantiana 6 days before culture results of the surgical specimen, allowing optimization of the empirical antifungal regimen, which led to a reduction in the size of the abscesses. LESSONS The authors’ findings suggest that microbial cfDNA sequencing may be particularly impactful in improving the management of brain abscesses in which the differential diagnosis is wide because of immunosuppression.

Chagas Disease (CD), a chronic infection caused by the

The COVID-19 pandemic sparked rapid development of SARS-CoV-2 diagnostics. However, emerging variants pose the risk for target dropout and false-negative results secondary to primer/probe binding site (PBS) mismatches. The Agena MassARRAY® SARS-CoV-2 Panel combines RT-PCR and MALDI-TOF mass-spectrometry to probe for five targets across N and ORF1ab genes, which provides a robust platform to accommodate PBS mismatches in divergent viruses. Herein, we utilize a deidentified dataset of 1,262 SARS-CoV-2-positive specimens from Mount Sinai Health System (New York City) from December 2020 through April 2021 to evaluate target results and corresponding sequencing data. Overall, the level of PBS mismatches was greater in specimens with target dropout. Of specimens with N3 target dropout, 57% harbored an A28095T substitution that is highly-specific for the alpha (B.1.1.7) variant of concern. These data highlight the benefit of redundancy in target design and the potential for target performance to illuminate the dynamics of circulating SARS-CoV-2 variants.

Venezuela is in the midst of a humanitarian crisis with a dangerous cocktail of hyperinflation, violence, minimal local food production, and policies that impact the nutrition for millions of Venezuelans. Independent data suggests that most Venezuelans are food insecure, with alarming rates of acute and chronic malnutrition, especially among children. A re-emergence of poverty-related intestinal parasitoses and anemia has aggravated their health. With little to no response from public authorities, Venezuela is now the lowest-ranked country in the world in deworming coverage. Modest independent and private epidemiological studies suggest prevalence rates as high as 60% in some regions. This article reviews public health policies regarding malnutrition and intestinal parasitoses and aims to provide a rational approach based on international recommendations for countries in crisis.

As the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic contin-ues to expand, healthcare resources globally have been spread thin. Now, the disease is rapidly spreading across South America, with deadly consequences in areas with already weakened public health systems. The Amazon region is particularly susceptible to the wide-spread devastation from Coronavirus disease 2019 (COVID-19) because of its immunologi-cally fragile native Amerindian inhabitants and epidemiologic vulnerabilities. Herein, we discuss the current situation and potential impact of COVID-19 in the Amazon region and how further spread of the epidemic wave could prove devastating for many Amerindian people living in the Amazon rainforest.

SummaryBackgroundSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection in patients with Coronavirus Disease 2019 (COVID-19) prominently manifests with pulmonary symptoms histologically reflected by diffuse alveolar damage (DAD), excess inflammation, pneumocyte hyperplasia and proliferation, and formation of platelet aggregates or thromboemboli. However, the mechanisms mediating these processes remain unclear.MethodsWe performed multicolor staining for viral proteins, and lineage cell markers to identify SARS-CoV-2 tropism and to define the lung pathobiology in postmortem tissues from five patients with fatal SARS-CoV-2 infections.FindingsThe lung parenchyma showed severe DAD with thromboemboli in all cases. SARS-CoV-2 infection was found in an extensive range of cells including alveolar epithelial type II/pneumocyte type II (AT2) cells (HT2-280), ciliated cells (tyr-α-tubulin), goblet cells (MUC5AC), club-like cells (MUC5B) and endothelial cells (CD31 and CD34). Greater than 90% of infiltrating immune cells were positive for viral proteins including macrophages and monocytes (CD68 and CD163), neutrophils (ELA-2), natural killer (NK) cells (CD56), B-cells (CD19 and CD20), and T-cells (CD3ε). Most but not all infected cells were positive for the viral entry receptor angiotensin-converting enzyme-2 (ACE2). The numbers of infected and ACE2-positive cells correlated with the extent of tissue damage. The infected tissues exhibited low numbers of B-cells and abundant CD3ε+T-cells consisting of mainly T helper cells (CD4), few cytotoxic T cells (CTL, CD8), and no T regulatory cell (FOXP3). Antigen presenting molecule HLA-DR of B and T cells was abundant in all cases. Robust interleukin-6 (IL-6) expression was present in most uninfected and infected cells, with higher expression levels observed in cases with more tissue damage.InterpretationIn lung tissues from severely affected COVID-19 patients, there is evidence for broad SARS-CoV-2 cell tropisms, activation of immune cells, and clearance of immunosuppressive cells, which could contribute to severe tissue damage, thromboemboli, excess inflammation and compromised adaptive immune responses.FundingThis work used the UPMC Hillman Cancer Center and Tissue and Research Pathology/Pitt Biospecimen Core shared resource, which is supported in part by award P30CA047904 from the National Cancer Institute, and by UPMC Hillman Cancer Center Startup Fund and Pittsburgh Foundation Endowed Chair in Drug Development for Immunotherapy to S.-J. Gao.HIGHLIGHTSWe provide an atlas of lung immunopathology of fatal SARS-CoV-2 infections, revealing:Unexpected broad cell tropism and infection of parenchymal, endothelial and immune cells by SARS-CoV-2, which are associated with massive tissue damage and thromboemboli;Clearance of immunosuppressive T-regulatory cells, and suppression of B cells and cytotoxic T cells;Extensive infiltration and activation of immune cells;Pronounced IL-6 expression in all types of infected and uninfected cells.Research in contextEvidence before this studyPulmonary symptoms reflected by diffuse alveolar damage (DAD), excess inflammation, pneumocyte hyperplasia and proliferation, formation of platelet aggregates, and thromboemboli are the pathological features of COVID-19. However, the mechanisms mediating these processes have not been elucidated. We searched PubMed up to September 15, 2020 using the keywords “coronavirus disease 2019”, “COVID-19”, “SARS-CoV-2”, “cell tropism”, “cell markers”, “inflammation”, “interleukin 6”, “immune response”, “immune suppression”, “immunofluorescence” and “immunohistochemistry”, with no language restrictions. Single cell RNA sequencing (scRNA-seq) has revealed extensive expression of SARS-CoV-2 receptor angiotensin-converting enzyme-2 (ACE2) in a large variety of cell types. However, only low levels of SARS-CoV-2 infection have been detected in macrophages, neutrophils, type II pneumocytes (AT2), and goblet, club, ciliated and endothelial cells by scRNA-seq and immunohistochemistry. COVID-19 blood samples contain high levels of inflammatory cytokines including interleukin-6 (IL-6), high levels of monocytes and neutrophils, and depletion of lymphocytes. There is no information on the cell types infected by SARS-CoV-2 and extent of infection, the precise producing cells of inflammatory cytokines, and the status of immune cells in lungs from fatal COVID-19 patients.Added value of this studyBy multicolor staining for viral proteins and lineage markers in lung tissues from five fatal COVID-19 patients, we reveal SARS-CoV-2 infection in an extensive range of cells including type II pneumocytes (HT2-280), and ciliated (tyr-α-tubulin), goblet (MUC5AC), club-like (MUC5B) and endothelial cells (CD31 and CD34), which is correlated with the extent of DAD and thromboemboli. SARS-CoV-2 infection is found in greater than 90% of infiltrating immune cells, including macrophages and monocytes (CD68 and CD163), neutrophils (ELA-2), natural killer cells (CD56), B-cells (CD19 and CD20), and T-cells (CD3ε). Most but not all infected cells were positive for ACE2. There are abundant macrophages, monocytes, neutrophils and natural killer cells but low numbers of B-cells and abundant CD3ε+T-cells consisting of mainly T helper cells (CD4), few cytotoxic T cells (CTL, CD8), and no T regulatory cell (FOXP3). Antigen presenting molecule HLA-DR of B and T cells was abundant in all cases. Robust IL-6 expression was present in most uninfected and infected cells, with higher expression levels observed in cases with more tissue damage.Implications of all the available evidenceIn lung tissues from severely affected COVID-19 patients, there is evidence for broad SARS-CoV-2 cell tropisms, hyperactive immune cells, and clearance of immune cells including immunosuppressive cells, which could contribute to severe tissue damage, thromboemboli, excess inflammation and compromised adaptive immune responses. These results have implications for development of treatments.

Alice-in-Wonderland syndrome (AIWS) is a perceptual disorder embracing a spectrum of self-experienced paroxysmal body image illusions including most commonly distortions of shape (metamorphopsia), size (macropsia or micropsia), distance (pelopsia or teleopsia), movement, and color among other visual and somesthetic distortions. Depersonalization, derealization, and auditory hallucinations have also been described. Recent reports suggest that infectious diseases are the predominant etiology for AIWS, especially among children. This article reviews current understanding regarding the association between infection and development of AIWS.

Chagas disease (CD) in the United States is severely underdiagnosed, due to an absence of systematic screening as part of routine healthcare. We screened 189 relatives of 86 existing patients and found a CD prevalence of 7.4%. Screening close relatives of previously diagnosed individuals can effectively identify new CD cases.

[This corrects the article DOI: 10.1371/journal.pntd.0008686.].

Human toxocariasis is a zoonotic parasitic disease that represents extensive morbidity in many countries. Caused by Toxocara canis and Toxocara cati, the clinical spectrum of this helminthiasis can be extended from asymptomatic forms up to life-threatening syndromes, such as the visceral larva migrans. Its epidemiology and burden is not clear; many times it is not diagnosed and, in most countries, it is not a notifiable disease. Some recent reviews have shown a large range of variability in terms of reported seroprevalence by countries. In this review, we summarized information regarding human toxocariasis burden of disease and control efforts in the region of the Americas.

Russell bodies are pink eosinophilic accumulations within plasma cells. To date, two hypotheses have attempted to elucidate the biological events behind the formation of these bodies. One theory sustains that such bodies constitute cytoplasmic accumulation of immunoglobulin derivatives contained in the perinuclear cistern of the smooth endoplasmic reticulum because of an increased synthesis or altered secretion. On the other hand, since its initial description in the medical literature, several authors have attributed the formation of such bodies to the presence of microorganisms such as in the case of Russell body gastritis and its association to Helicobacter pylori infection. In an attempt to possibly characterize the presence of an infectious organism, we performed a thorough biomolecular analysis on a case of a 69-year-old female presenting with Russell body duodenitis which, to the best of our knowledge, constitutes the second report of this clinical entity in the English literature. In light that the events behind formation of such bodies in H. pylori-negative individuals remain unclear, we hypothesize on the possible pathways that could have led to their reactive mechanical and immune derivation.

A 48 year-old African American woman presented to her physician complaining of a rapidly evolving epigastric and right upper quadrant abdominal pain. A PET-CT of the abdomen and pelvis demonstrated hypermetabolic, polypoid masses within the gallbladder and several tumors in the left lobe of the liver for which she underwent diagnostic laparoscopy. The gallbladder revealed a 3.5 × 3.3 × 2.4 tan-brown exophytic mass located at the fundus and growing into the lumen with multiple contiguous papillary projections arising from the mucosal surface. A concurrent large cell neuroendocrine carcinoma and papillary adenocarcinoma of the gallbladder was revealed histologically. There was shared reactivity to antibodies directed against the distinct antigens for each morphological component with transitional tumor cells (of both histological components) located at the areas where the two tumor types merged, revealing common immunoreactivity for carcinoembryonic antigen, cancer antigen 19-9, keratin 19, c-kit (cluster of differentiation protein 117 (CD117)) and epithelial cell adhesion molecule. Ultrastructurally, individual cells were demonstrated to have overlapping features of neuroendocrine and glandular differentiation. The aforementioned histological, ultrastructural and immunohistochemical profile is strongly suggestive of a biphenotypic stem/progenitor cell tumor of the gallbladder.

Background Lepidopterism derived from contact with arthropods and/or their products can result in adverse reactions that vary in severity from mild irritation to severe reactions including anaphylactic shock and death. Lepidopterism includes cutaneous and/or mucosal manifestations, systemic symptoms, or both mucocutaneous and systemic manifestations. Objective Epidemic outbreaks of dermatitis due to Hylesia sp. have been recorded in several countries of Latin America. The impact of climatic changes occurring presently on migrational and reproductive cycles of Hylesia metabus is also discussed in this study. Materials and methods In Venezuela, swarms of migrating H. metabus moths are histori- cally recognized as the causative agents of ''Caripito itch,'' a disease that has become an important public health problem. Results: In this review, we present a series of four case reports reflecting the wide clinical pleomorphism exhibited in lepidopterism by H. metabus. Conclusion Although dermatitis caused by these moths is usually resistant to all therapeutic treatment, individualization of therapy based on symptoms led to successful treatment in all four cases.

Lobomycosis is a chronic dermal infection that presents a wide spectrum of clinical- dermatological manifestations, mainly characterized by the development of keloid lesions as well as nodular, verrucoid and sometimes ulcerous forms. The etiological agent at an international level, according to the consensus nomenclature, has been called Loboa loboi, even though recently it has been accommodated as Lacazia loboi. The present review extensively covers the clinical-epidemiological aspects as well as the most outstanding historical aspects, including the Venezuelan experience and the presentation of two new cases, which substantiate the Amazon basin as an endemic area for the disease.

Primary cutaneous carcinosarcoma is a rare biphenotypic neoplasm exhibiting both epithelial and sarcomatous elements. Even though its origin and biological aspects remain poorly understood, it has been postulated that this tumor may arise from progenitor cells, which subsequently differentiate into distinct tumor components. We have investigated the histological and immunohistochemical staining patterns of a cutaneous carcinosarcoma case, as well as its ultrastructural aspects. In addition, sarcomatous and epithelial tumor components were separated by laser capture microdissection and subjected to targeted, high-depth, next-generation sequencing of a 46-cancer gene panel to asses the gene mutational pattern amongst both components. There were transitional cells at the epithelial/mesenchymal transition that labeled with putative progenitor cell markers (K19, c-kit, CD34 and Bcl-2). There was shared reactivity to antibodies directed against the progenitor cell marker EpCAM (epithelial cell adhesion molecule) in both components. Ultrastructurally, individual cells were demonstrated to have overlapping features of epithelial and mesenchymal differentiation. The mutational analysis revealed point mutations in exon 5 of TP53, which were identical in both the epithelial and sarcomatous components, and which were concordant with p53 expression at a tissue level. The aforementioned histological, ultrastructural, immunohistochemical and mutational pattern is strongly suggestive of a common clonal origin to the distinct elements of this tumor.

Leishmaniasis is a diverse group of vector-borne diseases caused by a subset of predominantly intracellular protozoal species of the genus Leishmania. Cutaneous disease may be subdivided into localized, intermediate, and diffuse forms. Intermediate cutaneous leishmaniasis is distributed widely in Latin America and is characterized by cutaneous lesions, which may be accompanied by mucosal disease and demonstrate a tendency toward chronicity and relapse as well as resistance to standard treatment regimens. Leishmania parasites of the subgenus Viannia have been identified as the major etiologic agent of this subset of infections. The present review provides a brief perspective on leishmaniasis followed by a review of classification, transmission, clinical presentation, and evolution of disease, immunology, and current treatment approaches for the intermediate/borderline disseminated subset of cutaneous leishmaniasis.

Chagas disease has emerged as an important health problem in the Americas and, with globalization, in other parts of the world. Drug therapy for this parasitic infection has remained largely ineffective, especially in chronic stages of the disease. However, developments in experimental therapy might signal an important advance for the management of patients with Chagas disease. Herein, we review studies on the potential use of the benzofuran derivatives amiodarone and dronedarone in patients with Chagas disease. These agents have a dual role, not only as primary antiarrhythmic drugs, but also as antiparasitic agents. We believe that this 'kill two birds with one stone' approach represents a new tactic for the treatment of Chagas disease using currently approved drugs.

Toxocariasis is a parasitic infection produced by helminths that cannot reach their adult stage in humans. For their etiological species (Toxocara canis and Toxocara cati), man is a paratenic host. Infection by such helminths can produce a variety of clinical manifestations, such as: visceral larvae migrans syndrome, ocular larvae migrans syndrome and covert toxocariasis. In the visceral larvae migrans syndrome, the organs that are mainly involved include liver, lungs, skin, nervous system, muscles, kidneys and the heart. Regarding the latter, the importance of cardiovascular manifestations in toxocariasis, as well as its clinical relevance, has increasingly begun to be recognized. The current article is based on a systematic information search, focused mainly on the clinical and pathological aspects of cardiovascular manifestations in toxocariasis, including its pathophysiology, laboratory findings, diagnosis and therapeutical options, with the objective of highlighting its importance as a zoonosis and its relevance to the fields of cardiovascular medicine in adults and children.

A 48 year-old African American woman presented to her physician complaining of a rapidly evolving epigastric and right upper quadrant abdominal pain. A PET-CT of the abdomen and pelvis demonstrated hypermetabolic, polypoid masses within the gallbladder and several tumors in the left lobe of the liver for which she underwent diagnostic laparoscopy. The gallbladder revealed a 3.5 × 3.3 × 2.4 tan-brown exophytic mass located at the fundus and growing into the lumen with multiple contiguous papillary projections arising from the mucosal surface. A concurrent large cell neuroendocrine carcinoma and papillary adenocarcinoma of the gallbladder was revealed histologically. There was shared reactivity to antibodies directed against the distinct antigens for each morphological component with transitional tumor cells (of both histological components) located at the areas where the two tumor types merged, revealing common immunoreactivity for carcinoembryonic antigen, cancer antigen 19-9, keratin 19, c-kit (cluster of differentiation protein 117 (CD117)) and epithelial cell adhesion molecule. Ultrastructurally, individual cells were demonstrated to have overlapping features of neuroendocrine and glandular differentiation. The aforementioned histological, ultrastructural and immunohistochemical profile is strongly suggestive of a biphenotypic stem/progenitor cell tumor of the gallbladder.

Lepidopterism derived from contact with arthropods and/or their products can result in adverse reactions that vary in severity from mild irritation to severe reactions including anaphylactic shock and death. Lepidopterism includes cutaneous and/or mucosal manifestations, systemic symptoms, or both mucocutaneous and systemic manifestations. Epidemic outbreaks of dermatitis due to Hylesia sp. have been recorded in several countries of Latin America. The impact of climatic changes occurring presently on migrational and reproductive cycles of Hylesia metabus is also discussed in this study.In Venezuela, swarms of migrating H. metabus moths are historically recognized as the causative agents of "Caripito itch," a disease that has become an important public health problem.In this review, we present a series of four case reports reflecting the wide clinical pleomorphism exhibited in lepidopterism by H. metabus.Although dermatitis caused by these moths is usually resistant to all therapeutic treatment, individualization of therapy based on symptoms led to successful treatment in all four cases.

Lobomycosis is a chronic dermal infection that presents a wide spectrum of clinical- dermatological manifestations, mainly characterized by the development of keloid lesions as well as nodular, verrucoid and sometimes ulcerous forms. The etiological agent at an international level, according to the consensus nomenclature, has been called Loboa loboi, even though recently it has been accommodated as Lacazia loboi. The present review extensively covers the clinical-epidemiological aspects as well as the most outstanding historical aspects, including the Venezuelan experience and the presentation of two new cases, which substantiate the Amazon basin as an endemic area for the disease.